Propranolol elimination by right and left fetal liver: studies in the intact isolated perfused fetal sheep liver.
Propranolol extraction in vivo by the left lobe of the fetal sheep liver is greater than that by the right lobe, and this may be due to the fact that oxygenation of the left lobe is greater than that of the right lobe. To explore this hypothesis, we studied the elimination of (R)-(+)-propranolol (PROP) by right and left lobes of the intact isolated perfused fetal sheep liver model, in which there is equal oxygenation of both liver lobes. After isolation of the liver, near-term fetal sheep livers (n = 11) were perfused (2.68 +/- 1.05 ml/g liver/min) in situ via the umbilical vein in a 1-liter recirculating system. PROP was infused (1.2 mg/hr) into the reservoir after an initial bolus dose (2.3 mg). Perfusate samples were taken from the common and right and left hepatic veins every 10 min for determination of PROP concentrations and oxygen consumption over the 180-min experimental period. Mean ductus venosus shunt through the liver was 42 +/- 21% of perfusate flow. Oxygen consumption was not significantly different between the left and right lobes of the liver (0.79 +/- 0.46 and 0.67 +/- 0.44 micromol/g liver/min, respectively, P > .05), nor was there any significant difference between lobes in PROP hepatic extraction at steady state (0.25 +/- 0.20 and 0.25 +/- 0.23, respectively, P > .05). This supports the hypothesis that the difference between lobes in PROP extraction in vivo may be due to the difference in degree of oxygenation of the left and right lobes that is known to be present in vivo.
Ring
J A
JA
University of Melbourne, Department of Medicine, and Victorian College of Pharmacy, Monash University, Melbourne, Australia.
Ghabrial
H
H
Ching
M S
MS
Shulkes
A
A
Smallwood
R A
RA
Morgan
D J
DJ
D000818:Animals; D005865:Gestational Age; D008099:Liver / Q000033:anatomy & histology / Q000098:blood supply / Q000196:embryology*; D010101:Oxygen Consumption; D010477:Perfusion; D011433:Propranolol / Q000378:metabolism* / Q000493:pharmacokinetics; D012756:Sheep
D011433:Propranolol